Lixuan Gui1, Fangqin Wu2, Xu Han1, Xiayun Dai1, Gaokun Qiu1, Jun Li1, Jing Wang1, Xiaoming Zhang1, Tangchun Wu1, Meian He3. 1. MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, Hubei, China. 2. Department of Cardiology, Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China. 3. MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, Hubei, China. Electronic address: hemeian@hotmail.com.
Abstract
OBJECTIVE: Genome-wide association studies have identified multiple genetic loci associated with coronary heart disease (CHD) risk. However, whether these loci could improve the CHD risk prediction is unclear. METHODS AND RESULTS: The present case-control study (1146 CHD cases and 1146 controls) genotyped 19 recently discovered SNPs that associated with CHD risk. As a result, 10 SNPs were successfully replicated with odds ratios (ORs) ranging from 1.16 to 1.78 (P = 4.6 × 10(-2) to 5.99 × 10(-6)). A genetic risk score was constructed to assess the combined effects of the susceptibility loci on CHD risk. Subject in the second tertile (OR = 1.32, 95% CI, 1.02-1.73, P = 3.84 × 10(-2)) and the third tertile (OR = 2.62, 95% CI, 2.00-3.43, P = 3.18 × 10(-12)) had an increased risk of CHD comparing with those in the first genetic risk score tertile after adjustment for traditional risk factors including family history of CHD. Addition of the genetic risk score to the traditional model significantly improved the net reclassification as measured by the net reclassification index (NRI) (4.82%, P = 0.0001), however, no significant improvement was observed in discrimination of CHD, the area under the receiver operating characteristic curve (AUC) increased from 0.811 to 0.822 (P = 0.18). CONCLUSIONS: A multilocus genetic risk score was associated with CHD risk in a Chinese Han population. This genetic risk score improved the net reclassification but not improved the CHD discrimination. The potential clinical use of this variations remains to be defined.
OBJECTIVE: Genome-wide association studies have identified multiple genetic loci associated with coronary heart disease (CHD) risk. However, whether these loci could improve the CHD risk prediction is unclear. METHODS AND RESULTS: The present case-control study (1146 CHD cases and 1146 controls) genotyped 19 recently discovered SNPs that associated with CHD risk. As a result, 10 SNPs were successfully replicated with odds ratios (ORs) ranging from 1.16 to 1.78 (P = 4.6 × 10(-2) to 5.99 × 10(-6)). A genetic risk score was constructed to assess the combined effects of the susceptibility loci on CHD risk. Subject in the second tertile (OR = 1.32, 95% CI, 1.02-1.73, P = 3.84 × 10(-2)) and the third tertile (OR = 2.62, 95% CI, 2.00-3.43, P = 3.18 × 10(-12)) had an increased risk of CHD comparing with those in the first genetic risk score tertile after adjustment for traditional risk factors including family history of CHD. Addition of the genetic risk score to the traditional model significantly improved the net reclassification as measured by the net reclassification index (NRI) (4.82%, P = 0.0001), however, no significant improvement was observed in discrimination of CHD, the area under the receiver operating characteristic curve (AUC) increased from 0.811 to 0.822 (P = 0.18). CONCLUSIONS: A multilocus genetic risk score was associated with CHD risk in a Chinese Han population. This genetic risk score improved the net reclassification but not improved the CHD discrimination. The potential clinical use of this variations remains to be defined.